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OBJECTIVES:. Respiratory failure secondary to COVID-19 is associated with morbidity and mortality. Current anti-inflammatory therapies are effective but are given systemically and have significant side effects. Furosemide has anti-inflammatory properties, can be administered by inhalation, and is inexpensive. We investigated the efficacy of nebulized furosemide as an adjunctive therapy for COVID-19 respiratory failure. DESIGN:. A double-blind, randomized, placebo-controlled trial. SETTING:. Multicenter ICU study. PATIENTS:. Adults requiring invasive mechanical ventilation secondary to COVID-19. INTERVENTION:. Patients were randomized within 48 hours of intubation to receive inhaled furosemide or placebo until day 28, death, or liberation from mechanical ventilation. MEASUREMENTS AND MAIN RESULTS:. The study was stopped early due to waning incidence of COVID-19; 39 patients were available for analysis with mean ± sd age of 70.5 (10.8) years, Acute Physiology and Chronic Health Evaluation II 26.1 (7.8) and Fio2 60.0% (21.9). Baseline characteristics were similar between the groups. For the primary outcome of change in Pao2/Fio2 ratio between day 1 and day 6, it was +31.4 (83.5) in the furosemide arm versus +20.1 (92.8) in the control (p = 0.58). For secondary outcomes, furosemide versus control: 60-day mortality was 48% versus 71% (p = 0.20), hospital stay was 25.6 (21.9) versus 27.4 (25.0) days, p = 0.94 and VFD was 6.0 (9.1) versus 3.1 (7.1), p value of equals to 0.28. A post hoc analysis of the hierarchical composite outcome, alive and ventilator-free favored furosemide. There were no adverse events. CONCLUSIONS:. In this trial of inhaled furosemide for COVID-19 respiratory failure, differences in Pao2/Fio2 ratio to day 6 and other clinical outcomes were not significantly different, although the trial was underpowered due to early termination. Given the favorable profile of inhaled furosemide, further study is warranted in disease states where acute pulmonary inflammation contributes to the underlying pathophysiology.

Background: Acute kidney injury (AKI) resulting in kidney replacement therapy is rising among critically ill adults. Long-term kidney replacement therapy and critical illness are independently linked to acute and prolonged cognitive impairment, and structural brain pathology. Poor regional cerebral oxygenation (rSO 2 ) may be a contributing factor. Objective: To assess the feasibility of testing the association between intradialytic rSO 2 and acute and long-term neurological outcomes. Design: Longitudinal observational study. Setting and Participants: We enrolled patients initiating continuous kidney replacement therapy or intermittent hemodialysis in the Kingston Health Sciences Centre (KHSC) Intensive Care Unit (ICU). Measurements and Methods: rSO 2 was monitored during the first 72 hours of continuous kidney replacement therapy or throughout each intermittent hemodialysis session. We measured acute neurological impairment by daily delirium screening and long-term neurocognitive outcomes using the Kinarm robot, Repeatable Battery for the Assessment of Neuropsychological Status, and brain magnetic resonance imaging. Results: Of 484 ICU patients, 26 met the screening criteria. Two declined, and 13 met at least one exclusion criteria. Eleven patients were enrolled. Eight died in ICU, one died 2 months after discharge, and one declined follow-up. Data capture rates were high: rSO 2 /vitals (91.3%), and delirium screening and demographics (100%). Longitudinal testing was completed in 50% (1 of 2) of survivors. Limitations: Enrollment was low due to a variety of factors, limiting our ability to evaluate long-term outcomes. Conclusion: rSO 2 and delirium data collection is feasible in critically ill patients undergoing kidney replacement therapy; high mortality limits follow-up.

The Indo-Pacific legume genus Serianthes was recently placed in the Archidendron clade (sensu Koenen et al. 2020), a subclade of the mimosoid clade in subfamily Caesalpinioideae, which also includes Acacia, Archidendron, Archidendropsis, Falcataria, Pararchidendron, Paraserianthes and Wallaceodendron. Serianthes comprises ca. 18 species, five subspecies and two varieties that are characterised by bipinnately compound leaves with alternate sessile leaflets, branched axillary corymbiform panicles and woody indehiscent pods. Generic relationships, as well as species relationships within genera in the Archidendron clade, remain uncertain. While the sister relationship between Serianthes and the genus Falcataria is strongly supported by molecular data, the distinction between Serianthes and the monotypic genus Wallaceodendron has been questioned, based on their similar flower and fruit morphologies. We combined three gene-enriched hybrid capture DNA sequence datasets (generated from the 964 mimobaits v1 probe set, the expanded 997 mimobaits v2 probe set and the GoFlag angiosperm 408 probe set) and used their overlapping markers (77 loci of the target exonic and flanking regions) to test the monophyly of Serianthes and to investigate generic relationships within the Archidendron clade using 55 ingoid plus two outgroup taxa. We show that Serianthes is monophyletic, confirm the Serianthes + Falcataria sister relationship to Wallaceodendron and recognise this combined clade as the Serianthes clade within the Archidendron clade. We also evaluated the use of overlapping loci across datasets in combination with concordance analyses to test generic relationships and further investigate previously unresolved relationships across the wider ingoid clade. Concordance analysis revealed limited gene tree conflicts near the tips of the Archidendron clade, but increased discordance at the base of the clade, which could be attributed to rapid lineage divergence (radiation) and/or incomplete lineage sorting.

With high equilibrium temperatures and tidally locked rotation, ultra-hot Jupiters (UHJs) are unique laboratories within which to probe extreme atmospheric physics and chemistry. In this paper, we present high-resolution dayside spectroscopy of the UHJ WASP-189 b obtained with the new Gemini High-resolution Optical SpecTrograph (GHOST) at the Gemini South Observatory. The observations, which cover 3 hr of post-eclipse orbital phases, were obtained during the instrument’s System Verification run. We detect the planet’s atmosphere via the Doppler cross-correlation technique, and recover a detection of neutral iron in the planet’s dayside atmosphere at a significance of 7.5 σ in the red arm of the data, verifying the presence of a thermal inversion. We also investigate the presence of other species in the atmosphere and discuss the implications of model injection/recovery tests. These results represent the first atmospheric characterization of an exoplanet with GHOST’s high-resolution mode, and demonstrate the potential of this new instrument in detecting and studying ultra-hot exoplanet atmospheres.

Abstract The size/volume of the brain’s ventricles is essential in diagnosing and treating many neurological disorders, with various forms of hydrocephalus being some of the most common. Initial ventricular size and changes, if any, in response to disease progression or therapeutic intervention are monitored by serial imaging methods. Significant variance in ventricular size is readily noted, but small incremental changes can be challenging to appreciate. We have previously reported using artificial intelligence to determine ventricular volume. The values obtained were compared with those calculated using the inaccurate manual segmentation as the “gold standard”. This document introduces a strategy to measure ventricular volumes where manual segmentation is not employed to validate the estimations. Instead, we created 3D printed models that mimic the lateral ventricles and measured those 3D models’ volume with a tuned water displacement device. The 3D models are placed in a gel and taken to the magnetic resonance scanner. Images extracted from the phantoms are fed to an artificial intelligence-based algorithm. The volumes yielded by the automation must equal those yielded by water displacement to assert validation. Then, we provide certified volumes for subjects in the age range (1–114) months old and two hydrocephalus patients.

IntroductionSepsis is a result of initial over-activation of the immune system in response to an infection or trauma that results in reduced blood flow and life-threatening end-organ damage, followed by suppression of the immune system that prevents proper clearance of the infection or trauma. Because of this, therapies that not only limit the activation of the immune system early on, but also improve blood flow to crucial organs and reactivate the immune system in late-stage sepsis, may be effective treatments. The tyrosine kinase FES may fulfill this role. FES is present in immune cells and serves to limit immune system activation. We hypothesize that by enhancing FES in early sepsis and inhibiting its effects in late sepsis, the severity and outcome of septic illness can be improved.Methods and analysisIn vitro and in vivo modeling will be performed to determine the degree of inflammatory signaling, cytokine production, and neutrophil extracellular trap (NET) formation that occurs in wild-type (WT) and FES knockout (FES-/-) mice. Clinically available treatments known to enhance or inhibit FES expression (lorlatinib and decitabine, respectively), will be used to explore the impact of early vs. late FES modulation on outcomes in WT mice. Bioinformatic analysis will be performed to examine FES expression levels in RNA transcriptomic data from sepsis patient cohorts, and correlate FES expression data with clinical outcomes (diagnosis of sepsis, illness severity, hospital length-of-stay).Ethics and disseminationEthics approval pending from the Queen’s University Health Sciences & Affiliated Teaching Hospitals Research Ethics Board. Results will be disseminated through scientific publications and through lay summaries to patients and families.

Abstract Farmer wildlife management practices are critical to conserve biodiversity and ecosystem functions across intensively used agricultural landscapes. Policies and initiatives aimed at encouraging these practices have generally focused on economic incentives, with limited effectiveness. Farmer identity theory addresses the emergence of norms, values and perceptions in farm management and can contribute to the development of policies and initiatives that engage more effectively with farmers and farming communities. Here we evaluate linkages between farmer identity and wildlife habitat management practices in the intensively farmed US state of Iowa. We conducted an exploratory factor analysis using data from a survey of over 1,300 Iowa farmers that asked their opinions on what constitutes ‘a good farmer’. We use logistic regression to model relationships between farmer identity factor scores and contextual variables against participation in a set of habitat management practices. Four ‘good farmer’ identity types were identified and labelled as productivist, soil conservationist, wildlife conservationist and civic‐minded. Logistic regression results indicated that these farmer identity types have highly divergent responses to wildlife habitat management practices among Iowa farmers. Recreational factors may supplement identity and are also influential towards habitat production on farms. We conclude that farmer identity theory offers a critical link between social and ecological processes on Iowa farms. The research presented here quantitatively associates farmer identity theory with wildlife habitat management, increasing our understanding of how wildlife habitat practices and individual‐level farmer identities interact. A free Plain Language Summary can be found within the Supporting Information of this article.

OBJECTIVES:. High-frequency data streams of vital signs may be used to generate individualized hemodynamic targets for critically ill patients. Central to this precision medicine approach to resuscitation is our ability to screen these data streams for errors and artifacts. However, there is no consensus on the best method for data cleaning. Our goal was to determine whether an error-checking algorithm developed for intraoperative use could be applied to high volumes of arterial line data in an ICU population. DESIGN:. Multicenter observational study. SETTING:. ICUs across Ontario, Canada. PATIENTS:. Nested cohort of ICU patients with shock and/or respiratory failure requiring invasive mechanical ventilation. INTERVENTIONS:. High-frequency blood pressure data was analyzed. Systolic, diastolic, and mean arterial pressure minute averages were calculated. For manual analysis, a trained researcher retrospectively reviewed mean arterial pressure data, removing values that were deemed nonphysiological. The algorithm was implemented and identified artifactual data. MEASUREMENTS AND MAIN RESULTS:. Arterial line data was extracted from 15 patients. A trained researcher manually reviewed 40,798 minute-by-minute data points, then subsequently analyzed them with the algorithm. Manual review resulted in the identification of 119 artifacts (0.29%). The optimized algorithm identified 116 (97%) of these artifacts. Five hundred thirty-seven data points were erroneously removed or modified. Compared with manual review, the modified algorithm incorporating absolute thresholds of greater than 30 and less than 200 mm Hg had 97.5% sensitivity, 98.7% specificity, and a Matthew correlation coefficient of 0.41. CONCLUSIONS:. The error-checking algorithm had high sensitivity and specificity in detecting arterial line blood pressure artifacts compared with manual data cleaning. Given the growing use of large datasets and machine learning in critical care research, methods to validate the quality of high-frequency data is important to optimize algorithm performance and prevent spurious associations based on artifactual data.

Background: Neurocognitive impairment is a common finding across the spectrum of kidney disease and carries important consequences for quality of life. We previously demonstrated that robotic technology can identify neurocognitive impairments not readily detectable by traditional testing in patients with acute kidney injury (AKI) and chronic kidney disease (CKD). Objective: The present study aimed to assess whether these quantifiable deficits in neurocognition differ based on a diagnosis of AKI, CKD, or kidney failure. Design: This was a cross-sectional analysis of participants previously enrolled in an observational study. Setting: Patients were enrolled at a tertiary academic hospital, Kingston Health Sciences Centre, Kingston, ON, Canada. Patients: Adults with AKI, CKD, or kidney failure. Measurements: Each participant underwent robotic neurocognitive assessment using the Kinarm: an interactive robotic device that uses a series of behavioral tasks involving movement of the upper limbs to precisely quantify neurocognitive impairment across a variety of neurocognitive domains. Methods: Multilevel modeling was used to determine the effect of Kinarm task type, kidney diagnostic group (AKI vs CKD vs kidney failure), and the interaction between the two, on neurocognitive performance. Results: A total of 104 participants within 1 year of an AKI event or with CKD category G3-5 were enrolled. We found that across all of the kidney diagnostic groups, participants performed worst on the Kinarm tasks of Reverse Visually Guided Reaching ( b = 0.64 [95% confidence interval = 0.42, 0.85]), Visually Guided Reaching ( b = 0.28 [0.07, 0.49]), and Trail Making ( b = 0.50 [0.28, 0.72]), relative to all other tasks. There were no significant differences in average performance across tasks based on kidney diagnostic group. However, diagnostic group and neurocognitive task type interacted to determine performance, such that patients with AKI performed worse than those with either CKD or kidney failure on the Reverse Visually Guided Reaching task. Limitations: Kinarm assessment was performed at a single time point, and the sample size itself was small, which may lead to the risk of a false-positive association despite the use of multilevel modeling. Our sample size also did not permit inclusion of the underlying etiology of kidney impairment as a covariate in our analyses, which may have also influenced neurocognitive function. Conclusions: In this study that utilized the Kinarm to assess neurocognitive function, patients with AKI demonstrated significantly worse neurocognitive functioning than patients with CKD or kidney failure on a task measuring executive function and visuomotor control.

Phylogenomic data increase the possibilities of resolving the evolutionary and systematic relationships among taxa. This is especially valuable in groups with few and homoplasious morphological characters, in which systematic and taxonomical delimitations have been traditionally difficult. Such is the case of several lineages within Bryophyta, like Orthotrichaceae, the second most diverse family of mosses. Members of tribe Orthotricheae are common in temperate and cold regions, as well as in high tropical mountains. In extratropical areas, they represent one of the main components of epiphytic communities, both in dry and oceanic or hyperoceanic conditions. The epiphytic environment is considered a hostile one for plant development, mainly due to its low capacity of moisture retention. Thus, the diversification of the Orthotrichaceae in this environment could be seen as striking. Over the last two decades, great taxonomic and systematic progresses have led to a rearrangement at the generic level in this tribe, providing a new framework to link environment to patterns of diversification. Here, we use nuclear loci targeted with the GoFlag 408 enrichment probe set to generate a well-sampled phylogeny with well-supported suprageneric taxa and increasing the phylogenetic resolution within the two recognized subtribes. Specifically, we show that several genera with Ulota-like morphology jointly constitute an independent lineage. Within this lineage, the recently described Atlantichella from Macaronesia and Western Europe appears as the sister group of Ulota bellii from Zealandia. This latter species is here segregated in the new genus Rehubryum. Assessment of the ecological and biogeographical affinities of the species within the phylogenetic framework suggests that niche adaptation (including climate and substrate) may be a key evolutionary driver that shaped the high diversification of Orthotricheae.

Background: Transcatheter aortic valve implantation (TAVI) is a routine procedure that is often performed on older adults that are high-risk patients with severe aortic stenosis. Patients after TAVI may experience neurological complications. However, there is a lack of objective neurological testing available for patients undergoing cardiac surgery. Objective: This brief communication seeks to explore the use of robotic technology to quantify distinctive patterns of visuospatial, sensorimotor, and cognitive functioning in patients undergoing TAVI. Methods: Patients undergoing TAVI were recruited for this prospective observational study. Prior to their procedure, study participants performed four robotic reaching tasks using the Kinarm robotic system. Patients repeated the assessment three months after their TAVI procedure. Significant changes in overall task score and parameters were determined. Results: Ten patients were recruited and included in this brief report. In a simple reaching task, patients show significant improvement in performance post-TAVI. However, patients do not improve nor worsen in a complex reaching task after TAVI. Similarly, patients demonstrate impairments in both trail making tasks before and after their TAVI procedure. Conclusions: This study captures the variability in neurological functioning in older patients undergoing TAVI. Robotic technology and quantified assessment procedures can be extremely valuable for detecting perioperative neurological impairments in this patient population.

We report on a chemo-dynamical analysis of SPLUS J142445.34−254247.1 (SPLUS J1424−2542), an extremely metal-poor halo star enhanced in elements formed by the rapid neutron-capture process ( r -process). This star was first selected as a metal-poor candidate from its narrowband S-PLUS photometry and followed up spectroscopically in medium resolution with Gemini-South/GMOS, which confirmed its low-metallicity status. High-resolution spectroscopy was gathered with GHOST at Gemini-South, allowing for the determination of the chemical abundances for 36 elements, from carbon to thorium. At [Fe/H] = −3.39, SPLUS J1424−2542 is one of the lowest-metallicity stars with measured Th and has the highest $\mathrm{log}\epsilon (\mathrm{Th}/\mathrm{Eu})$ observed to date, making it part of the “actinide-boost” category of r -process–enhanced stars. The analysis presented here suggests that the gas cloud from which SPLUS J1424−2542 formed must have been enriched by at least two progenitor populations. The light-element ( Z ≤ 30) abundance pattern is consistent with the yields from a supernova explosion of metal-free stars with 11.3–13.4 M _⊙ , and the heavy-element ( Z ≥ 38) abundance pattern can be reproduced by the yields from a neutron star merger (1.66 M _⊙ and 1.27 M _⊙ ) event. A kinematical analysis also reveals that SPLUS J1424−2542 is a low-mass, old halo star with a likely in situ origin, not associated with any known early merger events in the Milky Way.

This article explores patterns in teachers' reported correction of student language use in speech and writing. The authors use the concept of language correction in student writing and student speech as a proxy for prescriptive approaches to teaching about language. By conducting a large-scale survey of all language and literacy teachers from preschool through 12th grade across an entire state, the authors were able to identify patterns in teachers' approaches to teaching about language that smaller case studies and nuanced qualitative studies have not yet documented. They examine differences in teachers' self-reported correction of student language use across teacher characteristics and contexts such as grade levels taught, regions of the state, years of teaching experience, and whether teachers had taken a linguistics class. The authors identified marked differences in how elementary and secondary teachers report correcting student writing and speech. They found a small but significant difference in the impact of taking a linguistics class depending on grades taught. They note small but significant differences between reported correction of language for teachers in urban and rural contexts. They discuss implications for professional development on teaching about language targeted to the needs of teachers based on grade level, context, and experience.

Entrenched compartmentalisation of curriculum subjects and 'teaching to the test' can leave students with limited understanding of the nature and interaction of disciplines. The necessity of developing future teachers' epistemic insight (EI) and equipping them with strategies to address the gaps between subjects has been pushed to the fore by challenges that emerged during the pandemic. This article examines the extent to which epistemic insight is understood by Initial Teacher Education tutors and features in their programmes as well as their recommendations for increasing the inclusion of multidisciplinary approaches in education, based on qualitative and quantitative research. While initial findings revealed a poor understanding of EI, its importance was broadly acknowledged, and the follow-up survey revealed progress in the form of greater engagement with and inclusion of EI by tutors in teacher education. This research was done in the context of a new inspection framework distinguishing substantive and disciplinary knowledge.

This article reports on research done at Brigham Young University on supporting teaching with primary sources. It reviews the literature on primary source literacy and lessons gleaned from interviews with faculty to begin to identify the competencies necessary to teach the skills of primary source literacy. It breaks these competencies down into manageable groups, both for special collections professionals and for faculty. The areas of competency include (1) domain knowledge and primary source skills, (2) pedagogy and instructional design skills, and (3) communications and soft skills. The article also examines two particularly effective teaching techniques--scaffolding and modeling. It concludes with a call for further conversation about how to teach with primary sources.

During a period when secularization poses many challenges to religiously affiliated colleges and universities, several key factors have been identified that can support these institutions in effectively meeting those challenges. This article identifies four of the principal drivers of secularization and how they have manifested themselves over the course of the 20th century. Those drivers are changes in the composition of university leadership, faculty, and student body; a push to comply with the accepted standards for academic excellence and the secularization of knowledge; a desire to be more like mainstream colleges and universities; and the need to accommodate growing religious pluralism in society. The article also identifies important actions that can support religiously affiliated postsecondary institutions in staying connected to their founding religious traditions. These factors include a clearly articulated vision for the institution that is based in the religious tradition, university leadership that is supportive of maintaining the connection between institution and religious tradition, and a strong campus culture based in the values of the religious tradition. The article then uses the experiences of Brigham Young University as an example of how these factors work together to counter secularization. The leadership decisions and actions taken by The Church of Jesus Christ of Latter-day Saints and Brigham Young University President Howard S. McDonald (1945-1949) are offered as a case study that may provide insights to other institutions at a time when trends in the United States continue to shift toward secularization.